Aqueous Tissue Clearing Composition for 3D Imaging
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Solution Overview
Problem
Current tissue clearing methods for biological tissues are limited by structural distortion, slow processing times, incompatibility with archived tissues, and poor compatibility with high-resolution imaging, particularly for non-neural, non-osseous tissues, which require improved aqueous-based solutions that preserve tissue integrity and are suitable for 3D imaging.
Innovation Solution
The development of tissue clearing compositions comprising a homogenizing agent, a water-soluble refractive index adjusting agent, a lipid-soluble refractive index adjusting agent, and a borate compound, which work together to achieve rapid, single-step tissue clearing without structural distortion, enhancing transparency and compatibility with various imaging techniques.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If delipidation-assisted RI homogenization or organic solvent-based RI homogenization is used to achieve good tissue transparency, then tissue clearing efficacy is improved, but substantial tissue damage occurs and structural integrity is compromised
Solution Approach 1:
The patent changes the chemical parameters of the clearing composition by using aqueous-based surfactants instead of organic solvents, and by adjusting refractive index with compatible agents. This allows achieving tissue transparency (RI homogenization) without the harmful effects of organic solvents, thus resolving the contradiction between transparency and tissue damage
Solution Approach 2:
The patent applies different functional components locally to different tissue components: surfactants target lipid membranes for gentle clearing, while RI-adjusting agents specifically modify refractive index. This localized approach achieves transparency without overwhelming tissue damage, resolving the contradiction between clearing efficacy and structural preservation
2Object-affected harmful factors
If aqueous-based simple RI homogenization is used to preserve tissue integrity, then tissue damage is minimized, but tissue clearing efficacy is insufficient
Solution Approach 1:
The patent creates a composite clearing composition combining multiple aqueous-based components: surfactants for membrane interaction, RI-adjusting agents for refractive index homogenization, and optional enzymes or antioxidants. This composite approach achieves effective transparency while maintaining tissue integrity, resolving the contradiction between gentle treatment and clearing efficacy
Solution Approach 2:
The patent designs a multi-functional aqueous composition where surfactants provide both cleaning and RI adjustment, while additional components address multiple tissue properties simultaneously. This universal approach overcomes the limitations of simple aqueous methods while preserving tissue integrity
3Productivity
If existing clearing agents are used to clear tissues rapidly, then processing time is reduced, but multiple treatment steps are still required and compatibility with archived tissues is poor
Solution Approach 1:
The patent merges multiple functions into a single clearing composition: surfactant action, RI adjustment, and tissue protection all occur simultaneously in one treatment step. This eliminates the need for multiple sequential steps while achieving rapid clearing and broad compatibility, resolving the contradiction between speed and process simplicity
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The proposed solution enables rapid and effective tissue clearing, preserving the structural integrity of non-neural, non-osseous tissues, allowing for high-resolution 3D imaging and compatibility with archival tissues, while maintaining the integrity of lipid membranes and fluorescent signals.
Implementation Method 1
The overall process of tissue clearing can be viewed as tissue refractive index (RI) homogenization (that is, homogenizing or making more equal the refractive index of the tissue)
Data Source
AI summary
Investigation of fine tissue structures, such as those in non-neural, non-osseous tissues or organs, is best performed in intact tissue. Described herein are compositions and methods for clearing tissues for subsequent three-dimensional analysis. The compositions referred to herein as tissue clearing compositions are composed of four core components: (1) a homogenizing agent such as N-methylglucamine, urea, thiourea, guanidine, guanidinium chloride, lithium perchlorate, ethylenediamine, and derivatives thereof; (2) a water-soluble adjusting agent such as iohexol, sodium thiosulfate, polyethylene glycol, and derivatives thereof; (3) a lipid-soluble adjusting agent such as 2,2′-thiodiethanol, propylene glycol, and derivatives thereof; and (4) a borate compound such as boric acid, tetraboric acid, disodium tetraborate, and derivatives thereof. The disclosed tissue clearing compositions are particularly suitable for use with non-neural, non-osseous tissues or organs. The tissues or organs can be fresh, archived, or retrieved from paraffin wax-embedded tissues.